Our group has gained considerable experience in the conduct of sophisticated pharmacotherapy trials with naltrexone, and other medications, in alcohol dependent individuals. While naltrexone has found utility in the treatment of this condition, there is considerable room for improvement, since it does not work for everyone. One way to potentially enhance naltrexone's efficacy is to combine it with another medication having a unique pharmacological profile. Similar combination therapy approaches have been found useful in a number of medical conditions (e.g. hypertension, diabetes, depression). Differing from naltrexone, aripiprazole is an FDA approved medication for the treatment of psychotic disorders which works by stabilizing the dopamine system, a neurochemical system known to play a large role in reinforcement and addiction. Our experience with the use of aripiprazole in a clinical trial with alcoholics, during a sub-acute dosing and bar-lab study with neuroimaging in non-treatment seeking alcoholics, and from animal data, suggests that it would be a good medication to combine with naltrexone for treatment-seeking alcohol dependent individuals. Aripiprazole is well-tolerated and safe in actively drinking individuals, and also lacks many of the more serious adverse effects shown by medications working on brain dopamine (e.g., extrapyramidal effects and dyskinisias). As a prelude to this proposal, we have found aripiprazole to be well tolerated when combined with naltrexone in a small pilot study. While data collected so far indicate tolerability of this combination, further data are needed to explore the potential safety and efficacy of combining aripiprazole with naltrexone. Therefore, in this exploratory/pilot study, we propose to randomize 60 alcohol dependent individuals to receive either naltrexone, naltrexone plus aripiprazole, or their matching placebos over a 16-week treatment period. All individuals will receive 9 sessions of Medical Management as developed for the COMBINE Study. The primary outcome variable will be drinks per drinking day. Heavy drinking days, clinical global outcome, craving, compliance, adverse events, mood and other variables will also be assessed to evaluate the effects of the medication combination over naltrexone alone. If this medication combination is found effective in this exploratory study, a larger clinical trial will be planned. [unreadable] [unreadable] [unreadable]